4&#39;, 5&#39;-dihydrospiro [estr/androst-4-ene-17, 2&#39; (3&#39;h)-furan]-3 beta-ols and esters thereof



United States Patent No Drawing. Filed Oct. 19, 1964, Ser. No. 404,966Claims. (Cl. 260-23955) This invention relates to4,5'-dihydr0spiro[estr/androst-4-ene-17,2'(3H)-furan]-3fl-ols, estersthereof, and processes whereby these products can be prepared. Moreparticularly, this invention provides new, useful, and unobviouschemical compounds of the formula wherein X represents hydrogen or analkanoyl radical and R represents hydrogen or the methyl radical.

Among the alkanoyl radicals represented by X, especially lower alkanoylradicals are preferred, i.e., radicals of the formula Those skilled inthe art will recognize that lower alkyl radicals are monovalent,saturated, acyclic, straightor branched-chain, hydrocarbon groupingstypified by methyl, ethyl, propyl, isopropyl, butyl, isobutyl,sec-butyl, tert-butyl, pentyl, 'neopentyl, hexyl, isohexyl, heptyl, andthe like of empirical formula -C,,H wherein n represents a positiveinteger less than 8.

The compounds to which this invention relates are useful because oftheir valuable pharmacological properties. Thus, for example, they areestrogen antagonists, as also anti-protozoal agents especially effectiveagainst Tetralzymena gelleii.

Preparation of the subject compounds proceeds by reducing an appropriateketone of the formula 3,297,586 Patented Jan. 10, 1967 See invention isnot to be construed as limited thereby, either in spirit or in scope,since it will be apparent to those skilled in the art of organicsynthesis that many modifications, both of materials and of methods, maybe practiced without departing from the purpose and intent of thisdisclosure. Throughout the examples hereinafter set forth, temperaturesare given in degrees Centigrade and relative amounts of materials inparts by weight, except as otherwise noted.

Example 1 4,5 dihydrospiro'kstr 4 ene 17,2(3H)furan]- 35-0l.--To asuspension of parts of lithium aluminum tri-tert-butoxy hydride in 710parts of tetrahydrofuran at 5 under nitrogen is added, during 5 minuteswith agitation, a solution of 85 parts of 4,5'-dihydrosipor[ester-4-ene-17,2(3'R)-furan]-3-one (preparable by the procedure set forth inBelgian Patent Number 631,946) in 890 parts of tetrahydrofuran.Agitation at 5 is continued for 40 minutes after the addition iscomplete, whereupon the resultant mixture is allowed to warm to roomtemperature during one hour and then poured into a mixture of 200 partsof glacial acetic acid and 10,000 parts of water. The oil whichseparates congeals after 3 hours at 5, at which point it is filteredoff, washed with water, dried in air, and consecutively recrystallizedfrom hexane and ethyl acetate to give 4',5-dihydrospiro[estr-4-ene-17,2(3H)-furan]-3;8-ol, melting at -135". The product has the formulaExample 2 3,8 acet0xy-4',5'-dihydr0spiro[eslr 4-ene-17,2'(3H)- furan].Asolution of 33 parts of 4,5-dihydrospiro [estr-4-ene-17,2(3H)-furan]-3,B-ol in 350 parts of pyridine and 270 parts of acetic anhydride isallowed to stand at room temperatures for 19 hours, then mixed with10,000 parts of ice water. The gummy precipitate thrown down solidifieswhen the mother liquor is decanted and replaced with water. Theprecipitate is collected on a filter, washed thereon with water, driedin air, and twice recrystallized from hexane to give3,8-acetoxy-4Q5'-dihydropiro-[ester-4- ene-17,2(3H)-furan], melting at117-120". The product has the formula Example 3 4',5'dihydrospiro[andrst-4-ene-17,2(3H) furanl- 3,8-0l.-To a suspension of 55parts of lithium aluminum tri-tert-butoxy hydride in 425 parts oftetrahydrofuran at 5 under nitrogen is added, during minutes withagitation, a solution of approximately 66 parts of4,5-dihydrospiro[androst-4-ene-l7,2'(3'H) furan]-3-one (preparable bythe procedure set forth in Belgian Patent Number 631,946) in 425 partsof tetrahydrofuran. Agitation at 5 is continued for one hour after theaddition is complete, whereupon the resultant solution is allowed towarm to room temperature during 2 hours and then poured into a mixtureof 200 parts of glacial acetic acid and 8000 parts of water. Theprecipitate which forms is filtered off,

washed with water, and twice recrystallizedfirst from a mixture ofbenzene and hexane and then from benzene aloneto give 4,5',dihydrospiro[androst 4-ene-17,2 (3H)-furan]-3,8-ol, melting at l66170.The product has the formula Example 4 furan], melting at approximately102-103. duct has the formula The pro- CH C00 What is claimed is: 1. Acompound of the formula wherein X is selected from the group consistingof hydrogen and lower alkanoyl radicals and R is selected from the groupconsisting of hydrogen and the methyl radical.

2. 4',5'-dihydroxyspiro[estr-4-ene-17,2(3'H) furan]- 35-01.

3. 3B acetoxy 4',5' dihydrospiro[estr 4 ene-l7,2' (3'H)-furan].

4. 4,5' dihydrospiro[androst 4 ene 17,2'(3H)- furan]-3fi-ol. j

5. 3fl-acetoxy 4',5-dihydrospiro[androst 4-ene-17,2' (3H)-furan]. I

No references cited.

LEWIS GOTTS, ,Primary Examiner.

HENRY A. FRENCH, Assistant Examiner.

1. A COMPOUND OF THE FORMULA